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CLIC4 Function in the Epithelial-Mesenchymal Transition of Epithelial Odontogenic Lesions

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Abstract

Background

Odontogenic lesions constitute a heterogeneous group of lesions. CLIC4 protein regulates different cellular processes, including epithelial-mesenchymal transition and fibroblast-myofibroblast transdifferentiation. This study analyzed CLIC4, E-cadherin, Vimentin, and α-SMA immunoexpression in epithelial odontogenic lesions that exhibit different biological behavior.

Methods

It analyzed the immunoexpression of CLIC4, E-cadherin, and Vimentin in the epithelial cells, as well as CLIC4 and α-SMA in the mesenchymal cells, of ameloblastoma (AM) (n = 16), odontogenic keratocyst (OKC) (n = 20), and adenomatoid odontogenic tumor (AOT) (n = 8). Immunoexpressions were categorized as score 0 (0% positive cells), 1 (< 25%), 2 (≥ 25% - < 50%), 3 (≥ 50% - < 75%), or 4 (≥ 75%).

Results

Cytoplasmic CLIC4 immunoexpression was higher in AM and AOT (p < 0.001) epithelial cells. Nuclear-cytoplasmic CLIC4 was higher in OKC’s epithelial lining (p < 0.001). Membrane (p = 0.012) and membrane-cytoplasmic (p < 0.001) E-cadherin immunoexpression were higher in OKC, while cytoplasmic E-cadherin expression was higher in AM and AOT (p < 0.001). Vimentin immunoexpression was higher in AM and AOT (p < 0.001). Stromal CLIC4 was higher in AM and OKC (p = 0.008). Similarly, α-SMA immunoexpression was higher in AM and OKC (p = 0.037). Correlations in these proteins’ immunoexpression were observed in AM and OKC (p < 0.05).

Conclusions

CLIC4 seems to regulate the epithelial-mesenchymal transition, modifying E-cadherin and Vimentin expression. In mesenchymal cells, CLIC4 may play a role in fibroblast-myofibroblast transdifferentiation. CLIC4 may be associated with epithelial odontogenic lesions with aggressive biological behavior.

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Data Availability

The authors declare that the data supporting this study’s findings are available from the corresponding author upon reasonable request.

Code Availability

Not applicable.

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Authors and Affiliations

  1. Oral Pathology and Medicine, Postgraduate Program in Dental Sciences, Department of Dentistry, Federal University of Rio Grande do Norte, Natal, RN, Brazil

    Mariana Carvalho Xerez, Caio César da Silva Barros, Maurília Raquel de Souto Medeiros, Rodrigo Porpino Mafra, Éricka Janine Dantas da Silveira & Antonio de Lisboa Lopes Costa

  2. Department of Dentistry, Federal University of Rio Grande do Norte, Av. Salgado Filho, 1787, Lagoa Nova, Natal, CEP: 59056-000, RN, Brazil

    Hévio Freitas de Lucena, Éricka Janine Dantas da Silveira & Antonio de Lisboa Lopes Costa

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  1. Mariana Carvalho Xerez
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Contributions

M.C.X., C.C.S.B., and M.R.S.M.: conceptualization, investigation, data curation, writing—original draft, review, and editing. R.P.M.: formal analysis, writing—review & editing. H.F.L.: investigation, writing—review & editing. É.J.D.S. and A.L.L.C.: conceptualization, supervision, writing—review & editing. All authors read and approved the manuscript.

Corresponding author

Correspondence to Mariana Carvalho Xerez.

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All procedures performed in this study followed the ethical standards of the institutional and/or national research committee and the 1964 Helsinki Declaration and its later amendments. This study was approved by the Committee of Ethics in Research of Universidade Federal do Rio Grande do Norte (Approval No. 6.046.877).

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Xerez, M.C., da Silva Barros, C.C., de Souto Medeiros, M.R. et al. CLIC4 Function in the Epithelial-Mesenchymal Transition of Epithelial Odontogenic Lesions. Head and Neck Pathol 18, 40 (2024). https://doi.org/10.1007/s12105-024-01646-1

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